Scientists find common virus can kill cancer tumors in mice

Science

Scientists have wiped out tumors in mice using a common virus that apparently tricks cancer cells into self-destructing.

It is too early to know if the approach might work in humans. Many treatments that look promising in mice prove disappointing when they are tested on people.

However, the research sheds light on something scientists have noticed for years: Some viruses harm cancer cells but leave normal, healthy cells unscathed.

The research involves a virus that is believed to be harmless to humans, and a gene called p53 that normally suppresses tumors. In most cancer patients, the p53 gene is defective. The virus apparently zeroes in on that flaw.

Peter Beard, a professor of virology at the Swiss Institute for Experimental Cancer Research in Epalinges, said his team found that the explanation involves an unusual hairpin-like portion of the virus' DNA.

When a cancer cell encounters the virus, it apparently interprets the hairpin structure as damage to its own DNA. The cell tries to rid itself of the damage and ends up self-destructing.

As part of their research, the Swiss team injected human colon cancer cells into a group of laboratory mice, followed by the virus two days later. Only two of the 12 rodents later formed tumors.

In mice with existing colon cancer tumors, injections of the virus eliminated tumors in six of the 10 rodents.

The findings were reported in Thursday's issue of the journal Nature.

Beard said his team hopes to pinpoint the precise feature on the hairpin structure that sends cancer cells to their death. If they can do that, he said, it may be possible to specially engineer the virus or even develop a drug mimicking its effects.

The virus tested is one of six known adeno-associated viruses, a group of viruses that are among the smallest that exist. Some of those viruses have been used many times by scientists for gene therapy, in which a virus delivers a healthy copy of a gene to a patient. Such experiments have had mixed results.

Cancer researcher Arnold J. Levine, co-discoverer of the p53 gene in 1979 and president of Rockefeller University in New York, said the Swiss team's approach is a long way off from ever being tried in humans.

He said scientists pursuing therapies using viruses to target the p53 defect, including gene therapy, all face the same problem: how to efficiently deliver the therapy to every cancer cell in the body.

One problem with adeno-associated viruses is that they cannot reproduce without the help of another virus.

Levine said the research's main contribution is explaining why certain viruses can damage cancer cells while sparing normal cells.

''What this paper does is actually explain for the first time why cancer cells are preferentially knocked off by these viruses -- because they mimic DNA damage,'' Levine said. ''The cell apparently doesn't have the proper safeguards in place and it dies.''

The p53 gene mutation that the virus exploits is present in nearly 60 percent of all human cancers. It is the same vulnerability that also makes cancer cells prone to chemotherapy and radiation treatment, Beard said.

A scientist who helped develop an engineered virus, ONYX-015, that has shown promise in human clinical trials in destroying tumor cells with the mutated p53 gene called the new research ''very inventive.''

''The biggest question now is, can these viruses be grown in sufficient quantity to make human clinical testing possible? That will be the next step,'' said Frank McCormick, a professor of microbiology and immunology at the University of California at San Francisco.

On the Net:

Nature: www.nature.com

This article published in the Athens Banner-Herald on Thursday, August 30, 2001.